It has previously been shown that buffy coat platelet concentrates (BC-PCs) stored in a medium made up of approximately 70 percent platelet storage medium (Plasma-Lyte A, PL) and 30 percent plasma (BC-PC-P) are effective in vivo after 9 to 12 days of storage. In addition to sodium, potassium, magnesium, and chloride, PL contains 27 mM (27 mmol/L) sodium acetate and 23 mM (23 mmol/L) sodium gluconate. This study investigated the effect of acetate and gluconate on platelet metabolism. Identical BC-PCs were stored at 22 +/- 2-degrees-C in PL (BC-PC-P); PL with gluconate but without acetate, termed PL-A (BC-PC-A); or PL with acetate but without gluconate, termed PL-G (BC-PC-G). On Day 1 of storage, no significant differences were seen between the three groups of BC-PCs. In both BC-PC-P and BC-PC-G, pH and bicarbonate were stable at 7.0 +/- 0.03 and 8.4 +/- 0.9 mEq per L throughout 10 days of storage, whereas in BC-PC-A, they fell to 6.7 +/- 0.05 and 5.5 +/- 0.8 mEq per L on Day 5 (p < 0.0 1 vs. Day 1) and to 6.1 +/- 0.1 and 1.2 +/- 0.4 mEq per L, respectively, on Day 10. The buffering capacities of 70 percent PL, PL-A, or PL-G and 30 percent plasma were similar in a platelet-free setting when incremental additions of lactic acid were made. The role of acetate was further studied by adding C-14- or H-3-labeled acetate to BC-PC-P. On Day 7 of storage, radioactivity decreased to 79 +/- 1 percent of baseline in C-14-labeled BC-PC-P (p = 0.02), while it was unchanged in H-3-labeled BC-PC-P and in control samples in which C-14- and H-3-acetate were added to platelet-free plasma or PL. These studies indicate that platelets metabolize acetate to CO2 during storage and that acetate metabolism plays a major role in pH control during storage of BC-PCs.